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2005 Grant - Yan

Role of Mitochondrial Beta-Amyloid in Alzheimer's Disease

Shi Du Yan, M.D.College of Physicians and SurgeonsColumbia UniversityNew York, New York

2005 Zenith Fellows Award

The beta-amyloid protein fragment aggregates, or clumps together, outside cells. Evidence suggests that some aggregated forms of beta-amyloid may disrupt cell-to-cell communication and contribute to cell death. Other studies have shown, however, that elevated levels of beta-amyloid inside cells apparently occur early in the diseaseóbefore it aggregates outside cellsóand that these high internal concentrations may cause cellular dysfunction.

Shi Du Yan, M.D., and colleagues are investigating the impact of beta-amyloid on cellular structures called mitochondria, which use oxygen and nutrients to produce energy for a cell. The researchers have speculated that the accumulation of beta-amyloid inside mitochondria alters the function of energy-producing enzymes, the rate of oxygen consumption and the utilization of glucose (sugars).

In this study, the investigators will determine how beta-amyloid enters mitochondria, assess the effect of beta-amyloid on mitochondrial properties and characterize the subsequent impact on cell function. This work may help explain the mechanism of beta-amyloid toxicity and open new lines of investigation for therapies.